生物活性

• 靶点

  FGFR1 IC50:0.2nM

  FGFR2 IC50:2.5nM

  FGFR3 IC50:1.8nM

• 描述The FGFR (fibroblast growth factor receptor) family, comprising four members, FGFR1, FGFR2, FGFR3 and FGFR4, belongs to the RTKs which serve as high affinity receptors for FGFs controlling cell proliferation, migration, apoptosis and differentiation. AZD4547 is a highly potent inhibitor of FGFR1-3 with IC50 values of 0.2nM, 2.5nM, and 1.8nM and displays weaker activity against FGFR4 (IC50=165nM). AZD4547 has potent in vitro antiproliferative effects with IC50 values ranged from 18nM to 281nM, as well as inhibition on FGFR auto-phosphorylation downstream p-MAPK, p-FRS2 and p-PLCγ induced by FGF, on tumor cell lines with deregulated FGFR expression as KG1a expressing a truncated wild-type FGFR1 fusion protein, Sum52-PE cells expressing wild-type FGFR2 and KMS11 cells expressing translocated/Y373C mutated FGFR3 protein, but no effect on MCF7 cells with no identified defects in FGFR expression or signaling. Twice daily oral administration of AZD4547 at dose of 3mg/kg caused 53% tumor growth inhibition while doses of 12.5mg/kg once daily and 6.25 mg/kg twice daily resulted in complete tumor stasis in female SCID mice bearing KMS11 tumors. 12.5mg/kg once daily AZD4547 resulted in 65% tumor growth inhibition in KG1a model. The pharmacodynamic effect of AZD4547 can be shown by decreased p-FGFR3 in mice, within 15 minutes of drug administration^[1].
• 作用机制AZD4547 competes with ATP for binding to FGF receptors 1, 2 and 3, thus inhibiting autophosphorylation and downstream signaling.^[2]
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  4T1	-	Growth Inhibition Assay	-	IC50=0.64±0.11 μM	24642893
  4T1	1.25-20 μM	Apoptosis Assay	24 h	induces apoptosis dose dependently	24642893
  A549	0.1/1 μM	Cell viability Assay	48 h	enhances Erlotinib induced viability loss	26053020

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• 动物研究
  剂量	Mice: 1.5 mg/kg - 50 mg/kg[1] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02299999	Metastatic Breast Cancer	Phase 2	Recruiting	December 2022	France ... more >> Institut de Cancérologie de l'Ouest/Paul Papin Recruiting Angers, France Contact: Mario CAMPONE, MD       mario.campone@ico.unicancer.fr    Principal Investigator: Mario CAMPONE, MD          Institut Sainte-Catherine Recruiting Avignon, France Contact: Alice Mege, MD       a.mege@isc84.org    Principal Investigator: Alice Mege, MD          Polyclinique Bordeaux Nord Aquitaine Recruiting Bordeaux, France, 33077 Contact: Nadine DOHOLLOU, MD       n.dohollou@bordeauxnord.com    Contact: Nadine DOHOLLOU, MD          Institut Bergonié Recruiting Bordeaux, France Contact: Hervé Bonnefoi, MD       h.bonnefoi@bordeaux.unicancer.fr    Principal Investigator: Hervé Bonnefoi, MD          Centre François Baclesse Recruiting Caen, France Contact: Christelle Lévy, MD       c.levy@baclesse.unicancer.fr    Principal Investigator: Christelle Lévy, MD          Centre Jean Perrin Recruiting Clermont-Ferrand, France Contact: Marie-Ange Mouret Reynier, MD       marie-ange.mouret-reynier@cjp.fr    Principal Investigator: Marie-Ange Mouret Reynier, MD          Ch Alpes Leman Not yet recruiting Contamine Sur Arve, France, 74130 Contact: Carol ALLIOT, MD       calliot@ch-alpes-leman.fr    Contact: Carol ALLIOT, MD          Centre Georges François Leclerc Recruiting Dijon, France, 21079 Contact: Nicolas Isambert, MD       nisambert@cgfl.fr    Principal Investigator: Nicolas Isambert, MD          Chd Vendee Recruiting La Roche-sur-Yon, France, 85925 Contact: Tifenn L'Haridon, MD       tifenn.lharidon@chd-vendee.fr    Contact: Tifenn L'Haridon, MD          Centre Oscar Lambret Recruiting Lille, France Contact: Nuria KOTECKI, MD          Principal Investigator: Nuria KOTECKI, MD          Chu Dupuytren Not yet recruiting Limoges, France, 87000 Contact: Laurence VENAT-BOUVET, MD       laurence.venat-bouvet@chu-limoges.fr    Contact: Laurence VENAT-BOUVET, MD          Hopital Privé Jean Mermoz Not yet recruiting Lyon, France, 69008 Contact: Olfa DERBEL, MD       o.derbelmermoz@gmail.com    Contact: Olfa DERBEL, MD          Centre Hospitalier Lyon Sud Recruiting Lyon, France Contact: Benoit You, MD          Principal Investigator: Benoit You, MD          Centre Léon Bérard Recruiting Lyon, France Contact: Thomas Bachelot, MD       thomas.bachelot@lyon.unicancer.fr    Principal Investigator: Thomas Bachelot, MD          Institut Paoli Calmettes Recruiting Marseille, France Contact: Anthony Gonçalves, MD       goncalvesa@ipc.unicancer.fr    Principal Investigator: Anthony Gonçalves, MD          Institut Régional du Cancer Montpellier Val d'Aurelle Recruiting Montpellier, France Contact: William Jacot, MD       william.jacot@icm.unicancer.fr    Principal Investigator: William Jacot, MD          Centre Alexis Vautrin Recruiting Nancy, France Contact: Elisabeth Luporsi, MD       e.luporsi@nancy.unicancer.fr    Principal Investigator: Elisabeth Luporsi, MD          Institut de Cancérologie de l'Ouest/ René Gauducheau Recruiting Nantes, France Contact: Mario Campone, MD       mario.campone@ico.unicancer.fr    Principal Investigator: Mario Campone, MD          Centre Antoine Lacassagne Recruiting Nice, France Contact: Jean-Marc Ferrero, MD       jean-marc.ferrero@nice.unicancer.fr    Principal Investigator: Jean-Marc Ferrero, MD          Institut Curie Recruiting Paris, France Contact: Marie-Paule Sablin, MD       mariepaule.sablin@curie.fr    Principal Investigator: Marie-Paule Sablin, MD          Centre Eugène Marquis Recruiting Rennes, France Contact: Claudia Lefeuvre-Plesse, MD       c.lefeuvre@rennes.unicancer.fr    Principal Investigator: Claudia Lefeuvre-Plesse, MD          Centre Henri Becquerel Recruiting Rouen, France Contact: Jean-Christophe Théry, MD          Principal Investigator: Jean-Christophe Théry, MD          Institut Curie Recruiting Saint-Cloud, France Contact: Florence COUSSY, MD       florence.coussy@curie.fr    Principal Investigator: Florence COUSSY, MD          Hopitaux Universitaire de Strasbourg - Hopital Civil Recruiting Strasbourg, France Contact: Philippe BARTHELEMY, MD       philippe.barthelemy@chru-strasbourg.fr    Principal Investigator: Philippe BARTHELEMY, MD          Hopitaux Du Leman Recruiting Thonon-les-Bains, France, 74200 Contact: Francesco DEL PIANO, MD       f-delpiano@ch-hopitauxduleman.fr    Contact: Francesco DEL PIANO, MD          Institut Claudius Regaud Recruiting Toulouse, France Contact: Florence Dalenc, MD       dalenc.florence@iuct-oncopole.fr    Principal Investigator: Florence Dalenc, MD          Gustave Roussy Recruiting Villejuif, France Contact: Monica Arnedos, MD       Monica.ARNEDOS@gustaveroussy.fr    Principal Investigator: Monica Arnedos, MD          Sub-Investigator: Fabrice André, MD Collapse <<
  NCT02664935	Non-Small Cell Lung Cancer ... more >> Carcinoma, Squamous Cell Adenocarcinoma Collapse <<	Phase 2	Recruiting	September 2021	United Kingdom ... more >> Belfast City Hospital, Belfast Health and Social Care Trust Recruiting Belfast, United Kingdom Contact: Paula Scullin          Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust Recruiting Birmingham, United Kingdom, B15 2GW Contact: Gary Middleton, MB BS MD FRCP          Principal Investigator: Gary Middleton, MB BS MD FRCP          Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust Recruiting Birmingham, United Kingdom Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Recruiting Cambridge, United Kingdom, CB2 0QQ Contact: David Gilligan, BSc (Hons) MB BChir FRCP FRCR       cctc@addenbrookes.nhs.uk    Principal Investigator: David Gilligan, BSc (Hons) MB BChir FRCP FRCR          Velindre Cancer Centre, Velindre NHS Trust Recruiting Cardiff, United Kingdom, CF14 2TL Contact: Alison Brewster, BSC MB BCh FRCR MD    029 2061 5888       Principal Investigator: Alison Brewster, BSC MB BCh FRCR MD          Edinburgh Cancer Centre, Western General Hospital Recruiting Edinburgh, United Kingdom, EH4 2XU Contact: Melanie Mackean, MB ChB MRCP MSc MD          Principal Investigator: Melanie Mackean, MB ChB MRCP MSc MD          Royal Devon and Exeter Hospital Recruiting Exeter, United Kingdom Contact: Elizabeth Toy          Principal Investigator: Elizabeth Toy          Cancer Research UK Clinical Trials Unit, Beatson West of Scotland Cancer Centre Recruiting Glasgow, United Kingdom, G12 0YN Contact: Noelle O'Rourke, BA MB MCh MA MCRP MD FRCR CCST          Principal Investigator: Noelle O'Rourke, BA MB MCh MA MCRP MD FRCR CCST          St. James' University Hospital, Leeds Teaching Hospital NHS Trust Recruiting Leeds, United Kingdom, LS9 7TF Contact: Clive Mulatero, BA MB BCh MA PhD FRCP          Principal Investigator: Clive Mulatero, BA MB BCh MA PhD FRCP          Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust Recruiting Leicester, United Kingdom Contact: Dean Fennell          Royal Marsden Hospital, The Royal Marsden NHS Foundation Trust Recruiting London, United Kingdom, SW3 6JJ Contact: Sanjay Popat          Principal Investigator: Sanjay Popat, BSc MB BS MRCP PhD FRCP          Charing Cross Hospital, Imperial College Healthcare NHS Trust Recruiting London, United Kingdom Contact: Conrad Lewanski          Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust Recruiting London, United Kingdom Contact: James Spicer          St Bartholomew's Hospital, Barts Health NHS Trust Recruiting London, United Kingdom Contact: John Conibear          University College Hospital, University College London Hospitals NHS Foundation Trust Recruiting London, United Kingdom The Christie Hospital, The Christie NHS Foundation Trust Recruiting Manchester, United Kingdom Contact: Yvonne Summers          Sir Bobby Robson Cancer Trial Research Centre, The Newcastle upon Tyne Hospitals Recruiting Newcastle, United Kingdom, NE7 7DN Contact: Alastair Greystoke          Principal Investigator: Alastair Greystoke, BSc MBChB MRCP MSc PhD          Churchill Hospital, Oxford University Hospitals NHS Foundation Trust Recruiting Oxford, United Kingdom Contact: Denis Talbot          Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust Recruiting Sheffield, United Kingdom Contact: Sarah Danson          Southampton General Hospital, University Hospital Southampton NHS Foundation Trust Recruiting Southampton, United Kingdom, SO16 6YD Contact: Christian Ottensmeier       clinicaltrials@uhs.nhs.uk    Principal Investigator: Christian Ottensmeier Collapse <<
  NCT02117167	Non-small Cell Lung Cancer Met... more >>astatic Collapse <<	Phase 2	Recruiting	February 2022	France ... more >> Centre Hospitalier Henri Duffau Recruiting Avignon, France Contact: Nicolas CLOAREC, MD       nicolas.cloarec@ch-avignon.fr    Principal Investigator: Nicolas CLOAREC, MD          Centre Hospitalier Universitaire de Besancon - Hopital Jean Minjoz Recruiting Besancon, France Contact: Virginie WESTEEL, MD       virginie.westeel@univ.fcomte.fr    Principal Investigator: Virginie WESTEEL, MD          Hôpital Avicenne Recruiting Bobigny, France Contact: Boris DUCHEMANN, MD       boris.duchemann@aphp.fr    Principal Investigator: Boris DUCHEMANN, MD          Institut Bergonié Recruiting Bordeaux, France Contact: François Chomy, MD       f.chomy@bordeaux.unicancer.fr    Principal Investigator: François Chomy, MD          Hôpital Ambroise Paré Recruiting Boulogne Billancourt, France Contact: Etienne GIROUX LEPRIEUR, MD       etienne.giroux-leprieur@aphp.fr    Principal Investigator: Etienne GIROUX LEPRIEUR, MD          Hospices Civils de Lyon- Hôpital Louis Pradel Recruiting Bron, France Contact: Nicolas Girard, MD       nicolas.girard@chu-lyon.fr    Principal Investigator: Nicolas Girard, MD          Centre François Baclesse Recruiting Caen, France Contact: Radj Gervais, MD       r.gervais@baclesse.unicancer.fr    Principal Investigator: Radj Gervais, MD          CHU Caen Recruiting Caen, France Contact: Gérard Zalcman, MD       zalcman-g@chu-caen.fr    Principal Investigator: Gérard Zalcman, MD          Chu de Caen - Hopital Cote de Nacre Recruiting Caen, France Contact: Jeannick MADELAINE, MD       madelaine-j@chu-caen.fr    Principal Investigator: Jeannick MADELAINE, MD          Hôpital Louis Pasteur Recruiting Chartres, France Contact: Claire Lethrosne, MD       clethrosne@ch-chartres.fr    Principal Investigator: Claire Lethrosne, MD          centre Jean Perrin Recruiting Clermont-Ferrand, France Contact: Xavier Durando, MD       xavier.durando@cjp.fr    Principal Investigator: Xavier Durando, MD          CHU Clermont Ferrand - Hôpital Gabriel Montpied Recruiting Clermont-Ferrand, France Contact: Henri Janicot, MD       hjanicot@chu-clermontferrand.fr    Principal Investigator: Henri Janicot, MD          Hopitaux Civils de Colmar Recruiting Colmar, France Contact: Lionel MOREAU, MD       lionel.moreau@ch-colmar.fr    Principal Investigator: Lionel MOREAU, MD          Centre Hopsitalier Intercommunal de Créteil Recruiting Créteil, France Contact: Isabelle Monnet, MD       isabelle.monnet@chicreteil.fr    Principal Investigator: Isabelle Monnet, MD          Centre Georges François Leclerc Recruiting Dijon, France Contact: Bruno Coudert, MD       bcoudert@cgfl.fr    Principal Investigator: Bruno Coudert, MD          CHU Grenoble Recruiting Grenoble, France Contact: Denis Moro-Sibilot, MD       Dmoro-Sibilot@chu-grenoble.fr    Principal Investigator: Denis Moro-Sibilot, MD          Chd Vendee Recruiting La Roche Sur Yon, France Contact: Tifenn L'HARIDON, MD          Principal Investigator: Tifenn L'HARIDON, MD          CH du Mans Recruiting Le Mans, France Contact: Olivier Molinier, MD       omolinier@ch-lemans.fr    Principal Investigator: Olivier Molinier, MD          Centre Oscar Lambret Recruiting Lille, France Contact: Eric Dansin, MD       e-dansin@o-lambret.fr    Principal Investigator: Eric Dansin, MD          CHRU de Lille Recruiting Lille, France Contact: Alexis Cortot, MD       Alexis.CORTOT@CHRU-LILLE.FR    Principal Investigator: Alexis Cortot, MD          Centre Léon Bérard Recruiting Lyon, France Contact: Maurice Pérol, MD       maurice.perol@lyon.unicancer.fr    Principal Investigator: Maurice Pérol, MD          Hôpital Nord Recruiting Marseille, France Contact: Fabrice Barlesi, MD       fabrice.barlesi@ap-hm.fr    Principal Investigator: Fabrice Barlési, MD          Institut Paoli Calmettes Recruiting Marseille, France Contact: Anne MADROSZYK, MD       madroszyka@ipc.unicancer.fr    Principal Investigator: Anne MADROSZYK, MD          Institut de cancérologie de l'Ouest Recruiting Nantes, France Contact: Jaafar Bennouna, MD       jaafar.bennouna@ico.unicancer.fr    Principal Investigator: Jaafar Bennouna, MD          Centre Antoine Lacassagne Recruiting Nice, France Contact: Josiane OTTO, MD       josiane.otto@nice.unicancer.fr    Principal Investigator: Josiane OTTO, MD          Chr Orleans Recruiting Orleans, France Contact: Hugues MOREL, MD       hugues.morel@chr-orleans.fr    Contact: , MD          Principal Investigator: Hugues MOREL          AH-HP Hôpital Saint Louis Recruiting Paris, France Contact: Damien Pouessel, MD       damien.pouessel@sls.aphp.fr    Principal Investigator: Damien Pouessel, MD          AP-HP Hôpital Cochin Recruiting Paris, France Contact: Jeanne Chapron, MD       jeanne.chapron@cch.aphp.fr    Principal Investigator: Jeanne Chapron, MD          AP-HP Hôpital Européen Georges Pompidou Withdrawn Paris, France AP-HP Hôpital Tenon Recruiting Paris, France Contact: Marie Wislez, MD       marie.wislez@tnn.aphp.fr    Principal Investigator: Marie Wislez, MD          Institut Curie Recruiting Paris, France Contact: Catherine Daniel, MD       catherine.daniel@curie.fr    Principal Investigator: Catherine Daniel, MD          Centre Hospitalier de Pau Recruiting PAU, France Contact: Aldo RENAULT, MD       aldo.renault@ch-pau.fr    Principal Investigator: Aldo RENAULT, MD          Centre Hospitalier Lyon Sud Recruiting Pierre Bénite, France Contact: Jean-Pierre Souquet, MD       pierre-jean.souquet@chu-lyon.fr    Principal Investigator: Jean-Pierre Souquet, MD          CHR Pontchailloux Withdrawn Rennes, France Chru Strasbourg - Nouvel Hopital Civil Recruiting Strasbourg, France Contact: Philippe BARTHELEMY, MD          Principal Investigator: Philippe BARTHELEMY, MD          CHI de Toulon - Hôpital Sainte-Musse Recruiting Toulon, France Contact: Xavier TCHIKNAVORIAN, MD          Principal Investigator: Xavier TCHIKNAVORIAN, MD          CHU Toulouse -Hôpital Larrey Recruiting Toulouse, France Contact: Julien Mazières, MD       mazieres.j@chu-toulouse.fr    Principal Investigator: Julien Mazières, MD          Hôpital Bretonneau Recruiting Tours, France Contact: Eric Pichon, MD       e.pichon@chu-tours.fr    Principal Investigator: Eric Pichon, MD          Gustave Roussy Recruiting Villejuif, France Contact: Benjamin Besse, MD       Benjamin.BESSE@gustaveroussy.fr    Principal Investigator: Benjamin Besse, MD          Sub-Investigator: Jean-Charles Soria, MD Collapse <<

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• 参考文献

• [1] Gavine PR, Mooney L, et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012 Apr 15;72(8):2045-56.